Highlights • Immunotherapy has emerged as a new approach to treat cancer patients. • Nivolumab and Pembrolizumab have received approval for melanoma, NSCLC and RCC. • Despite their enthusiastic ...results, their high costs suggest careful consideration. • The cooperation between clinicians and economists will be crucial in future years. • This will guarantee economic sustainability and access to care for all patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Hyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the incidence and relative risk (RR) in ...cancer patients treated with these agents.
The scientific literature regarding hyponatraemia was extensively reviewed using MEDLINE, PubMed, Embase and Cochrane databases. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% Confidence Intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies.
4803 potentially relevant trials were identified: of them, 13 randomized phase III studies were included in this meta-analysis. 6670 patients treated with 8 targeted agents were included: 2574 patients had hepatocellular carcinoma, whilst 4096 had other malignancies. The highest incidences of all-grade hyponatraemia were observed with the combination of brivanib and cetuximab (63.4) and pazopanib (31.7), while the lowest incidence was reported by afatinib (1.7). The highest incidence of high-grade hyponatraemia was reported by cetuximab (34.8), while the lowest incidences were reported by gefitinib (1.0). Summary RR of developing all-grade and high-grade hyponatraemia with targeted agents was 1.36 and 1.52, respectively. The highest RRs of all-grade and high-grade hyponatraemia were associated with brivanib (6.5 and 5.2, respectively). Grouping by drug category, the RR of high-grade hyponatraemia with angiogenesis inhibitors was 2.69 compared to anti-Epidermal Growth Factor Receptors agents (1.12).
Treatment with biological therapy in cancer patients is associated with a significant increased risk of hyponatraemia, therefore frequent clinical monitoring should be emphasized when managing targeted agents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rectal cancer accounts for a relevant part of colorectal cancer cases,with a mortality of 4-10/100000 per year.The development of locoregional recurrences and the occurrence of distant metastases ...both influences the prognosis of these patients.In the last two decades,new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival.Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates.The employment of neoadjuvant treatment,delivered before surgery,also achieved an improved local control and an increasedsphincter preservation rate in low-lying tumors,with an acceptable acute and late toxicity.This review describes the multidisciplinary management of rectal cancer,focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.
Highlights • Neuroendocrine tumors of the gastro-entero-pancreatic system (GEP-NETs) are a heterogeneous group of neoplasms, with different
behavior. • A shared therapeutic sequence for GEP-NET ...treatment still does not exist. • The aim of this review is to identify the first and further better approaches among all available therapeutic options.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Introduction
Melanoma is one of the most common cancers in younger people. The incidence of cutaneous melanoma is increasing in patients of both sexes, with female patients generally living longer ...than their male counterparts. The aim of this retrospective study was to evaluate and confirm the sex-based difference in survival of melanoma patients and the relationship of this difference with pathological features.
Methods
A total of 1023 patients who had been treated at the Department of Medical Oncology, Università Politecnica Marche (Ancona, Italy) and the INRCA-IRCCS Department of Dermatology (Ancona, Italy) between 1987 and 2014 were enrolled in the study.
Results
In terms of stage of disease at onset, there was a significant difference in disease-free survival (DFS) and overall survival (OS) in favor of female patients in disease stage I (
P
= 0.001 and
P
= 0.01, respectively) and II (
P
= 0.02 and
P
= 0.009, respectively). Female patients also showed a significant improvement in 12-year DFS and 12-year OS adjusted for pathological features (Breslow thickness, ulceration, “absent” tumor-infiltrating lymphocyte (TIL) melanomas, “non-brisk” TIL pattern). Globally, female patients had an advantage over with male patients in both DFS and OS (
P
< 0.001).
Conclusions
Our results show that women have a survival benefit over with men after adjustment for many variables that can reduce mortality risk in female melanoma patients. In a future investigation we wish to examine possible biological sex differences in tumor–host interactions.
Background This investigation evaluated whether the performance at a preoperative symptom-limited stair-climbing test was a prognostic factor in resected pathologic stage I non-small cell lung cancer ...(NSCLC). Methods Observational analysis was performed on a prospective database that included 296 patients who underwent pulmonary lobectomy for pathologic stage T1 N0 or T2 N0 NSCLC (2000 to 2008). Patients who received induction chemotherapy were excluded. Survival was calculated by the Kaplan-Meyer method. The log-rank test was used to assess differences in survival between groups. The relationships between survival and baseline and clinical variables were determined by Cox multivariate analyses. Results Median follow-up was 43 months. The best cutoff associated with prognosis was an 18-meter stair climb. Median (months) survival and 5-year survival of patients who climbed more than 18 meters were significantly longer than those who climbed less than 18 meters (97 vs 74; 77% vs 54%, p = 0.001). Cox regression model (hazard ratio) showed that climbing more than 18 meters (0.5; p = 0.003), diffusion capacity of the lung for carbon monoxide (0.98; p = 0.02), and pT stage (1.8; p = 0.02) were independent prognostic factors. Patients who climbed less than 18 meters had increased deaths from cancer (24% vs 15%, p = 0.1) or other causes (19% vs 9%, p = 0.02). Conclusions Preoperative cardiopulmonary fitness is a significant prognostic factor in patients after resection for early-stage NSCLC. Interventions aimed at improving exercise tolerance can be useful to improve long-term prognosis after NSCLC operations.
Role of maspin in cancer Berardi, Rossana; Morgese, Francesca; Onofri, Azzurra ...
Clinical and translational medicine,
7/3, Volume:
2, Issue:
1
Journal Article
Peer reviewed
Open access
Maspin (mammary serine protease inhibitor), is a member of the serine protease inhibitor/non-inhibitor superfamily. Its expression is down-regulated in breast, prostate, gastric and melanoma cancers ...but over-expressed in pancreatic, gallbladder, colorectal, and thyroid cancers suggesting that maspin may play different activities in different cell types. However, maspin expression seems to be correlated with better prognosis in prostate, bladder, lung, gastric, colorectal, head and neck, thyroid and melanoma cancer. In breast and ovarian cancer maspin significance is associated with its subcellular localization: nucleus maspin expression correlates with a good prognosis, whilst in pancreatic cancer it predicts a poor prognosis. Since tumor metastasis requires the detachment and invasion of tumor cells through the basement membrane and stroma, a selectively increased adhesion by the presence of maspin may contribute to the inhibition of tumor metastasis. Furthermore the different position of maspin inside the cell or its epigenetic modifications may explain the different behavior of the expression of maspin between tumors. The expression of maspin might be useful as a prognostic and possibly predictive factor for patients with particular types of cancer and data can guide physicians in selecting therapy. Its expression in circulating tumor cells especially in breast cancer, could be also useful in clinical practice along with other factors, such as age, comorbidities, blood examinations in order to select the best therapy to be carried out. Focusing on the malignancies in which maspin showed a positive prognostic value, therapeutic approaches studied so far aimed to re-activate a dormant tumor suppressor gene by designed transcription factors, to hit the system that inhibits the expression of maspin, to identify natural substances that can determine the activation and the expression of maspin or possible “molecules binds” to introduce maspin in cancer cell and gene therapy capable of up-regulating the maspin in an attempt to reduce primarily the risk of metastasis.
Further studies in these directions are necessary to better define the therapeutic implication of maspin.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 ...thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.
Neuroendocrine tumors (NETs) represent a spectrum of rare neoplasms arising in different organism sites. Depending on the site of onset, they also can be distinguished using lab exams (secretingvs. ...nonsecreting), clinical symptoms (functioningvs. nonfunctioning), behavioral, morphological characteristics (tumor cells’ architectural growth patterns, mitotic and Ki-67 index, presence of necrosis), and grade of cellular differentiation. The aim of this review is to focus on the main signaling pathways targeted by medical treatments of advanced sporadic gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) neuroendocrine neoplasms. The scientiifc literature regarding treatment of advanced GEP and BP-NETs has been extensively reviewed using MEDLINE and PubMed databases, selecting principal and more recent research articles, clinical trials, and updated guidelines. Somatostatin analogues represent a valid approach to control symptoms in functioning tumors and to inhibit tumor progression in certain categories on the basis of the typical somatostatin receptor expression observed in NETs. The pathogenesis of NETs has been the subject of increased interest in recent years. Many driver mutations pathway genes have been identiifed as important factors in the carcinogenesis process and, therefore, as potential targets for new anticancer therapies. Activating mutations have been shown in epidermal growth factor receptor, stem cell factor receptor, platelet-derived growth factor receptor, vascular endothelial growth factor, basic-ifbroblastic growth factor, transforming growth factor, insulin-like growth factor-1, and their receptors. Effective M-Tor inhibition pathway modulation has led to the approval of drugs in this ifeld such as everolimus. New drugs and several combination regimens with targeted and newer biological agents are being developed and tested in recently conducted and ongoing trials.
Panitumumab is the first fully human monoclonal antibody to Epidermal Growth Factor Receptor (EGFR) to enter clinical trials for the treatment of solid tumors. The anti-tumor activity of panitumumab ...has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in numerous cancer models, particularly lung, kidney and colorectal (CRC). Preclinical and clinical studies have established a role for panitumumab in metastatic colorectal cancer (mCRC) refractory to multiple chemotherapeutic regimens. Based on these encouraging findings, panitumumab was approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing mCRC refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. The improvement in progression free survival (PFS) and response rate (RR) produced by panitumumab monotherapy was significantly greater in patients with non mutated (wild-type) K-RAS than in those with mutant K-RAS. Therefore implementing routine K-RAS screening and limiting the use of EGFR inhibitors to patients with wild-type K-RAS appears the better strategy for select only the patients who could benefit from the therapy with panitumumab and also may have the potential for cost savings. The purpose of this review was to evaluate the patient-related, disease-related and economic-related evidence for the use of panitumumab in the treatment of metastatic colorectal cancer in clinical practice.
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